It has been reported in recent years that a ligand of GPR40, which is one of the G Protein-Coupled Receptors (GPCR), is fatty acid and GPR40 in pancreatic β cell is deeply involved in insulin secretion action (Nature, 2003, vol. 422, pages 173-176). Thus, a GPR40 agonist promotes insulin secretion, a GPR40 antagonist inhibits insulin secretion, and the agonist and the antagonist are useful as an agent for the treatment of type 2 diabetes, obesity, impaired glucose tolerance, insulin resistance, neurodegenerative diseases (Alzheimer's disease) and the like (WO03/068959 and WO02/057783).
On the other hand, many compounds useful as an agent for the treatment of diabetes have been reported.
For example, WO02/092590 discloses that a peroxisome proliferator activated receptor (PPAR) modulator represented by the formula:
wherein X1: a C1-3 alkyl and the like; R1, R2: H and the like; R3, R4, R5: H, CH3 and the like; R26, R27: H and the like; m: 0-3; X2: O and the like; R6, R7: H and the like; Y, Z: one is CH and the other is S or O; R8: a phenyl and the like; and R9: a C1-6 alkyl and the like,is useful as an agent for the prophylaxis or treatment of PPAR mediated disease (e.g., diabetes).
WO02/053547 discloses that an alkanoic acid derivative represented by the formula:
wherein R1: an optionally substituted 5-membered aromatic heterocyclic group; X: a bond, O, S, —NR6— (R6: H, an optionally substituted hydrocarbon group and the like) and the like; Q: a divalent C1-20 hydrocarbon group; Y: a bond, O, S, —NR7— (R7: H, an optionally substituted hydrocarbon group and the like) and the like; ring A: an aromatic ring optionally further having 1 to 3 substituents; Z: —(CH2)n-Z1- (n: 1-8, Z1: O and the like) and the like; ring B: a benzene ring optionally further having 1 to 3 substituents, and the like; U: a bond and the like; W: a divalent C1-20 hydrocarbon group; and R3: —OR8— (R8: H, an optionally substituted hydrocarbon group) or —NR9R10— (R9, R10: H, an optionally substituted hydrocarbon group and the like) and the like; provided that when ring B is a benzene ring optionally further having 1 to 3 substituents, then U is a bond,is useful as an agent for the prophylaxis or treatment of diabetes, hyperlipidemia, impaired glucose tolerance and the like.
WO99/11255 discloses that a compound represented by the formula:
wherein R1: a C1-8 alkyl, a C1-8 alkoxy, a halogen atom, a trifluoromethyl and the like; R2: —COOR3 (R3: H, a C1-4 alkyl) and the like; A: a C1-8 alkylene and the like; G: a carbon ring optionally substituted by a C1-8 alkyl, a C1-8 alkoxy, a halogen atom, a trifluoromethyl or a nitro, and the like; E1: a C1-8 alkylene and the like; E2: —O— and the like; E3: a single bond and the like; n: 0, 1; and Cyc1 ring: absent and the like, has a PPAR receptor regulating action, and is useful as an agent for the prophylaxis or treatment of metabolism abnormality diseases such as diabetes, obesity, syndrome X, hypercholesterolemia, hyperlipoproteinemia and the like, and the like.
WO00/64876 discloses that a compound represented by the formula:
wherein ring ArI, ring ARII, ring ArIII: an optionally substituted condensed ring and the like; A: —O—, —S—, a bond, —NR13— (R13: H, an alkyl and the like) and the like; B: —O— and the like; D: a bond, an ethylene; E: a bond, an ethylene; Z: R21O2C—, (R21)2NCO— (R21: H, an alkyl and the like) and the like; a, b, c, e: 0-4; d: 0-5; f: 0-6; and R1-R12: H and the like, is useful as a PPAR ligand receptor binder, PPAR receptor agonist or PPAR receptor antagonist, and can be used as an agent for the treatment of diabetes.
WO01/00603 discloses that a compound represented by the formula:
wherein X: COOH (containing ester) and the like; X1: CH2 and the like; dotted line shows double bond only when X1 is CH; X2: O and the like; R1, R2: H, Me and the like; n: 1, 2; Y, Z: one is N and the other is S or O; y: an integer of 0-5; and R3: CF3 and the like,can be used as a PPARδ agonist, and is useful as an agent for the prophylaxis or treatment of PPARδ mediated disease (e.g., hyperlipidemia, arteriosclerosis, type I or II diabetes and the like).
WO97/31907 discloses that a compound represented by the formula:
wherein A: a 5- to 6-membered heterocycle containing at least one heteroatom selected from O, N and S, and the like; B: a C1-6 alkylene and the like; ALK: a C1-3 alkylene; R1: H, a C1-3 alkyl; and Z: —(C1-3 alkylene)phenyl optionally substituted by a halogen and the like,is useful as a PPARγ agonist, and can be used as an agent for the prophylaxis or treatment of hyperglycemia, type I or II diabetes, hyperlipidemia and the like.
WO02/083616 discloses that a compound represented by the formula:
wherein Ar: a phenyl substituted by 1 to 5 the same or different halogen atoms and the like, and the like; R1: a halogen atom and the like; R2: H and the like; R3, R4: H, a halogen atom; m: 1, 2; and n: 2-7,has a superior insulin sensitizing action, hypoglycemic action, hypolipidemic action, antiinflammatory action, immunomodulating action, lipoperoxide production suppressive action and PPAR activating action, and is useful as an agent for the treatment of diabetes.
WO01/55085 discloses that a compound represented by the formula:
wherein A: an aryl optionally substituted by OH and the like; X1, X2: H and the like; Y, Z: H and the like; n: 0-3; m: 0, 1; Q: O and the like; Ar: an arylene and the like; and R1-R4: H and the like,is useful as an agent for the treatment of PPAR related diseases, and useful as an agent for the treatment of, for example, type 2 diabetes, impaired glucose tolerance, insulin resistance, hypertriglyceridemia and the like.
However, it has not been disclosed at all that these known therapeutic drugs for diabetes have a GPR40 receptor function modulating action, and there is no report on a compound having a GPR40 receptor function modulating action (compound useful as a GPR40 agonist or GPR40 antagonist). Under the circumstances, development of a compound having a GPR40 receptor function modulating action has been desired.